AIMS: The goal of this application is to competitively renew Dr. Jian-Ying Wang's Senior Research Career Scientist (SRCS) Award, and to continuously support Dr. Wang's VA research program. NOMINEE: Dr. Wang has held a position of Senior Research Career Scientist from 2011, and he also holds the title of Professor in the Departments of Surgery and Pathology at University of Maryland School of Medicine (UMSOM) at Baltimore. Dr. Wang's research program has been continuously funded by VA- MERIT Review Awards and multiple NIH-R01 grants for more than twenty-two years. Dr. Wang has had many seminal research accomplishments throughout his career, and published more than 140 peer- reviewed original research articles that have created more than 5,000 citations. In addition, Dr. Wang is a major mentor/sponsor for VA Career Development Awards, and he also acts as a co-investigator in several currently active VA-sponsored research projects. RESEARCH: Studies in Dr. Wang's laboratory are to investigate the mechanisms underlying gut mucosal regeneration and rapid epithelial restitution after acute injury; and to further search for new and more effective therapies to maintain the intestinal epithelial integrity in patients with critical illness. Defective regulation of early intestinal mucosal restitution and subsequent disruption of the gut epithelial integrity occur commonly in various pathological states such as: stress/peptic ulcerations, Crohn's disease/ulcerative colitis, post-massive surgery, trauma, and sepsis. Since the exact mechanisms underlying gut mucosal continuous regeneration and rapid mucosal repairs after acute injury are still obscure; effective therapies to preserve the gut epithelial integrity are limited, especially in patients with critical surgical illnesses. Dr. Wang's research program is highly focused on the regulation of rapid gut mucosal repair and homeostasis by Ribonucleic acid ( RNA)-binding proteins (RBPs) and noncoding RNAs (ncRNAs) in health and surgical diseases. His research program studies stress-related processes regulated by RBPs and ncRNAs, the post-translational events that affect target gene expression in the presence or absence of cellular polyamines, and the interplay between RBPs and ncRNAs under physiological and pathological conditions. Dr. Wang's research employs the state-of-the-art techniques, including approaches that examine specific messenger (m)RNA/ncRNA or mRNA/RBP interactions as well as approaches focused on large-scale RNA analyses. His group has also extensively used gain-of- function transgenic and tissue-specific knockout approaches to generate various genetically modified animal models. Importantly, Dr. Wang's research projects are directly relevant to surgical patients with mucosal injury/delayed healing, maladaptation, barrier dysfunction, inflammation, and sepsis. The overarching goal of Dr. Wang's research program is to elucidate the post-transcriptional processes that govern gut mucosal regeneration and rapid epithelial restitution, and to create a fundamental base for development of new therapeutics for gut mucosal injury-related diseases. IMPACT: Dr. Wang's research program directly addresses an important health issue relevant to the VA mission, since gut mucosal injury-related diseases such as stress/peptic ulcerations, Crohn's disease/ulcerative colitis, and gut barrier dysfunction occur commonly in our VA patient population. Dr. Wang also actively collaborates with a number of investigators in the VA Maryland Health Care System (VAMHCS) Research Service, and his expertise and academic activity help moving the VAMHCS research program forward.